| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
| Targets |
SSRI; tricyclic antidepressant (TCA)
|
|---|---|
| ln Vitro |
Pipofezine Dihydrochloride Monohydrate 2 [1]
The MicroED structure 2 was solved in a monoclinic P 21/c space group at the resolution of 0.82 Å (Figure 2b and Figure 3), with the unit cell parameters of a = 6.88 Å, b = 15.61 Å, c = 15.93 Å, α = 90.0°, β = 97.2°, γ = 90.0°. Two conforms, namely 2a and 2b were identified in the uniFig t cell. Each can be transformed by inversion symmetry or 180° rotation of C11‒N4/C11′‒N4′ bond. The crystal packing is formed mainly by hydrogen bonds and ion-dipole interactions between 2a/2b and chloride anions along b- and c-axes, i.e. hydrogen bonds N5/N5′─H···Cl1 (3.01 Å) and N3/N3′─H···O2 (2.67 Å); ion-dipole interactions between CH atoms and chloride anions (Figure S3, Supporting Information). The water molecules serve as hydrogen bond donors to Cl1 or Cl2 anions that bridge 2a and 2b molecules together (Figure S3, Supporting Information). The packing along the a-axis is facilitated by strong parallel-displaced pi-stacking interactions between the phenyl and pyridazine rings in 2a and 2b (3.65 Å). In 2, bond angles are mostly fixed, with only one freely rotating bond (C10‒C11‒N4‒C15 and C10′‒C11′‒N4′‒C15′, measured at ±178.60° in 2a and 2b), generating a co-planar arrangement of piperazine ring and tricyclic moiety (Figure S4, Supporting Information).[5]
|
| Enzyme Assay |
2‒hSERT Complexes[1]
2 was tested at the central (S1) and allosteric (S2) sites in hSERT (Figure S12c, Supporting Information),[32] however the final docking center was found near S2 site due to the weak binding observed in S1 site (i.e., only the hydrophobic interactions). A salt bridge between Asp98 and piperazine ring, together with one pi-stacking (Phe335), one pi-cation interaction (Arg104), and three hydrophobic interactions (Phe335, Phe556) to the tricyclic moiety stabilized the binding complex of 2/hERT (Figure 4c). The structures of 2 in its drug-formulation state and biologically active state are very similar, with only 3–6° rotation C11′‒N4′ bond (Figure S4, Supporting Information), and maintain the piperazine ring and tricyclic moiety in a nearly co-planar geometry (C10‒C11‒N4‒C15≈180°) for both states. The minimum conformational changes ensure small entropy differences upon binding which is beneficial for the binding of 2 to the receptor.
|
| References |
|
| Additional Infomation |
Most treatments to alleviate major depression work by either inhibiting human monoamine transporters, vital for the reuptake of monoamine neurotransmitters, or by inhibiting monoamine oxidases, which are vital for their degradation. The analysis of the experimental 3D structures of those antidepressants in their drug formulation state is key to precision drug design and development. In this study, microcrystal electron diffraction (MicroED) is applied to reveal the atomic 3D structures for the first time of five of the most prevalent antidepressants (reboxetine, pipofezine, ansofaxine, phenelzine, and bifemelane) directly from the commercially available powder of the active ingredients. Their modes of binding are investigated by molecular docking, revealing the essential contacts and conformational changes into the biologically active state. This study underscores the combined use of MicroED and molecular docking to uncover elusive drug structures and mechanisms to aid in further drug development pipelines.[1]
|
| Molecular Formula |
C16H23CL2N5O2
|
|---|---|
| Molecular Weight |
388.2921
|
| Exact Mass |
387.122
|
| CAS # |
63302-99-8
|
| Related CAS # |
Azaphen;24853-80-3
|
| PubChem CID |
2728833
|
| Appearance |
Light yellow to green yellow solid powder
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
7
|
| Rotatable Bond Count |
1
|
| Heavy Atom Count |
25
|
| Complexity |
387
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
VKMOGSQJNTXLNA-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C16H19N5O.2ClH.H2O/c1-19-7-9-21(10-8-19)15-11-13-16(18-17-15)22-14-6-4-3-5-12(14)20(13)2;;;/h3-6,11H,7-10H2,1-2H3;2*1H;1H2
|
| Chemical Name |
5-methyl-3-(4-methylpiperazin-1-yl)pyridazino[3,4-b][1,4]benzoxazine;hydrate;dihydrochloride
|
| Synonyms |
63302-99-8; Azaphen dihydrochloride monohydrate; Azaphen (dihydrochloride monohydrate); Azaphenonxazine dihydrochloride monohydrate; 5-Methyl-3-(4-methylpiperazin-1-yl)-5H-benzo[B]pyridazino[4,3-E][1,4]oxazine dihydrochloride hydrate; 5-methyl-3-(4-methylpiperazin-1-yl)pyridazino[3,4-b][1,4]benzoxazine;hydrate;dihydrochloride; Azafen dihydrochloride monohydrate; Cambridge id 5175311;
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
H2O : ≥ 100 mg/mL (~257.54 mM)
DMSO : ~1 mg/mL (~2.58 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (128.77 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5754 mL | 12.8770 mL | 25.7539 mL | |
| 5 mM | 0.5151 mL | 2.5754 mL | 5.1508 mL | |
| 10 mM | 0.2575 mL | 1.2877 mL | 2.5754 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
